BACKGROUND Infections after placement of cardiac implantable electronic devices (CIEDs) are associated with substantial morbidity and mortality. There is limited evidence on prophylactic strategies, other than the use of preoperative antibiotics, to prevent such infections. METHODS We conducted a randomized, controlled clinical trial to assess the safety and efficacy of an absorbable, antibiotic-eluting envelope in reducing the incidence of infection associated with CIED implantations. Patients who were undergoing a CIED pocket revision, generator replacement, or system upgrade or an initial implantation of a cardiac resynchronization therapy defibrillator were randomly assigned, in a 1:1 ratio, to receive the envelope or not. Standard-of-care strategies to prevent infection were used in all patients. The primary end point was infection resulting in system extraction or revision, long-term antibiotic therapy with infection recurrence, or death, within 12 months after the CIED implantation procedure. The secondary end point for safety was procedure-related or system-related complications within 12 months. RESULTS A total of 6983 patients underwent randomization: 3495 to the envelope group and 3488 to the control group. The primary end point occurred in 25 patients in the envelope group and 42 patients in the control group (12-month Kaplan-Meier estimated event rate, 0.7% and 1.2%, respectively; hazard ratio, 0.60; 95% confidence interval [CI], 0.36 to 0.98; P = 0.04). The safety end point occurred in 201 patients in the envelope group and 236 patients in the control group (12-month Kaplan-Meier estimated event rate, 6.0% and 6.9%, respectively; hazard ratio, 0.87; 95% CI, 0.72 to 1.06; P<0.001 for noninferiority). The mean (±SD) duration of follow-up was 20.7±8.5 months. Major CIED-related infections through the entire follow-up period occurred in 32 patients in the envelope group and 51 patients in the control group (hazard ratio, 0.63; 95% CI, 0.40 to 0.98). CONCLUSIONS Adjunctive use of an antibacterial envelope resulted in a significantly lower incidence of major CIED infections than standard-of-care infection-prevention strategies alone, without a higher incidence of complications. (Funded by Medtronic; WRAP-IT ClinicalTrials.gov number, NCT02277990.).

The impact of bacterial genetic characteristics on the outcome of patients with Staphylococcus aureus infections is uncertain. This investigation evaluated potential associations between bacterial genotype and clinical outcome using isolates collected as part of an international phase 2 clinical trial (FAST II) evaluating telavancin for the treatment of complicated skin and skin structure infections (cSSSI). Ninety S. aureus isolates from microbiologically evaluable patients with cSSSI enrolled in the FAST II trial from 11 sites in the United States (56 isolates, or 62%) and 7 sites in South Africa (34 isolates, or 38%) were examined for staphylococcal cassette chromosome mec, agr, and the presence of 31 virulence genes and subjected to pulsed-field gel electrophoresis (PFGE). South African methicillin-susceptible S. aureus (MSSA) isolates were more likely to carry certain virulence genes, including sdrD (P ‫؍‬ 0.01), sea (P < 0.01), and pvl (P ‫؍‬ 0.01). All 44 (49%) methicillin-resistant S. aureus (MRSA) isolates were from the United States; 37 (84%) were strain USA 300 by PFGE. In the United States, MRSA isolates were more likely than MSSA isolates to carry genes for sdrC (P ‫؍‬ 0.03), map/eap (P ‫؍‬ 0.05), fnbB (P ‫؍‬ 0.11), tst (P ‫؍‬ 0.02), sea (P ‫؍‬ 0.04), sed (P ‫؍‬ 0.04), seg (P ‫؍‬ 0.11), sej (P ‫؍‬ 0.11), agr (P ‫؍‬ 0.09), V8 (P ‫؍‬ 0.06), sdrD, sdrE, eta, etb, and see (P < 0.01 for all). MRSA isolates were more often clonal than MSSA isolates by PFGE. Isolates from patients who were cured were significantly more likely to contain the pvl gene than isolates from patients that failed or had indeterminate outcomes (79/84 [94%] versus 3/6 [50%]; P ‫؍‬ 0.01). S. aureus strains from different geographic regions have different distributions of virulence genes.

In Brazil, where Leishmania chagasi causes endemic American visceral leishmaniasis (AVL), the spread and maintenance of human disease are attributed to canine reservoirs. However, despite measures directed toward the elimination of infected canines, the incidence of human disease continues to increase. To evaluate the role of infected canines in the acquisition of AVL by humans, we undertook a controlled intervention study in three similar, but isolated, valleys of Pancas, Espírito Santo, Brazil. In the two experimental (intervention) valleys, infected dogs were eliminated whereas in the control valley, seropositive canines remained untouched. During the 12-month study period, human seropositivity rates, as measured by dot enzyme-linked immunosorbent assay, increased from 15% to 54% in the intervention valleys and from 14% to 54% in the control valley. The elimination of infected canines in the intervention valleys did not result in a statistically significant difference between the incidences of human serological conversion in the intervention and control valleys at either 6 (20% and 22%, respectively; P = .5961) or 12 months (26% and 27%, respectively; P = .9442). The role of humans as a significant reservoir for AVL is proposed as an explanation for the study results.